Conformation of peptides constructed from achiral amino acid residues Aib and ΔZPhe: Computational study of the effect of L/D- Leu at terminal positions

✍ Scribed by Fateh Singh Nandel; Baldeep Khare

• Publisher: Wiley (John Wiley & Sons)
• Year: 2004
• Tongue: English
• Weight: 196 KB
• Volume: 77
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.20128

✦ Synopsis

Abstract

Conformational studies of the peptides constructed from achiral amino acid residues Aib and Δ^Z^Phe (I) Ac‐Aib‐Δ^Z^Phe‐NHMe (II), and Ac‐(Aib‐Δ^Z^Phe)~3~‐NHMe; peptides III–VI having L‐Leu or D‐Leu at either the N‐ or the C‐terminal position and of peptides VII–X having Leu residues in different enantiomeric combinations at both the N‐ and the C‐terminal positions in peptide II have been studied to design the peptide with the required helical sense. Peptide II, as expected, adopts degenerate left‐ and right‐handed helical structures. It has been shown that the peptides IV and VI having D‐Leu at either the N or the C terminus can be realized in the right‐handed helical structure with the ϕ,ψ values of −20° and −60° for the Aib/Δ^Z^Phe residues. L‐Leu and D‐ Leu at both the terminals in peptides VII and VIII, respectively, have hardly any effect as both the left‐ and the right‐handed structures are found to be degenerate. Peptides III and IX can be realized in right‐ and left‐handed helical structures, respectively, in solvents of low polarity whereas peptides V and X are predicted to be in the right‐handed helical structures stabilized by carbonyl–carbonyl interactions without the formation of hydrogen bonds. The conformational states with the ϕ,ψ values of 0° and −85° in peptide V are characterized by rise per residue of 2.03 Å, rotation per residue of 117.5°, and 3.06 residues per turn. In all peptides having Leu residue at the N terminus, the methyl moiety of the acetyl group is involved in the CH/π interactions with the CϵCδ edge of the aromatic ring of Δ^Z^Phe (3) and the amino group NH of Δ^Z^Phe is involved in the NH/π interactions with its own aromatic ring. The CH~3~ groups of the Aib residues are also involved in CH/π interactions with the i + 1th and i + 3th Δ^Z^Phe's aromatic side chains. © 2004 Wiley Periodicals, Inc. Biopolymers, 2005